Abstract

Variance of time-of-flight distributions have been shown to be more sensitive to cerebral blood flow (CBF) during dynamic-contrast enhanced monitoring of neurotrauma patients than attenuation. What is unknown is the degree to which variance is affected by changes in extracerebral blood flow. Furthermore, the importance of acquiring the arterial input function (AIF) on quantitative analysis of the data is not yet clear. This animal study confirms that variance is both sensitive and specific to changes occurring in the brain when measurements are acquired on the surface of the scalp. Furthermore, when the variance data along with the measured AIF is analyzed using a nonparametric deconvolution method, the recovered change in CBF is in good agreement with CT perfusion values.

Figures (6)

A depiction of the time-to-peak (TTP) method. Hypothetical tissue and arterial concentration curves including the effects of dye recirculation are shown by the solid black lines, along with their corresponding TTP values (TTPC and TTPCa, respectively). The solid grey lines represent the first moments of the concentration curves without the effects of recirculation.

The relationship between changes in tissue-curve TTP (ΔTTPC) and changes in CBF (ΔCBF) (grey lines). (A) The effect of varying the relationship between CBV and CBF, which was performed using the Grubb relationship for γ = 0.2, 0.4 and 0.6, and setting TTPCa = 0. (B) The effect of varying the arterial TTP (TTPCa) from 0 to 6 s with γ set to 0.38. The solid lines show the negative unity slope for comparison.

Representative curves from one animal (pig #2) under the four conditions. In this case, the thickness of the extracerebral layer was 10.2 mm. (A) Change in attenuation (ΔA) for measurements made on intact scalp (solid grey), ischemic scalp (dashed grey), skull (dashed black) and brain (solid black). (B) Change in variance (ΔV) for the same conditions. (C) ΔA measured on the brain (solid black) compared with ΔV measured on the scalp (dashed black).

Box-and-whisker plot of the difference in measured blood flow indices during the extracerebral manipulations compared to measurements acquired on the brain. Each parameter was evaluated from seventeen measurements acquired in four pigs. Boxes are bound by 1st and 3rd quartiles, with the centre line indicating the median. Error bars represent the range of the data, and crosses signify outliers. Only ΔA dBF was significantly different from the expected change of zero (p < 0.001). Additionally, none of ΔA TTP, ΔV TTP, or ΔV dBF differed significantly from each another, as measured by a paired t-test.

Representative curves from one animal under normocapnia (solid lines) and hypocapnia (dashed lines). (A) The change in attenuation (ΔA) made on intact scalp for the two conditions. (B) The change in variance (ΔV) made on intact scalp for the two conditions. (C) ΔA measured directly on the brain for the two conditions. Note: curves have been normalized to the maximum of the normocapnia curve.

Tables (2)

Table 2 Percent change in the blood flow indices (TTP and dBF) obtained by analysis of attenuation (ΔA) and variance (ΔV) of DTOF during hypocapnia. Measurements were obtained directly on the brain and on the contralateral scalp. The error values are relative to the CBF change measured by CT perfusion (CTP). The thickness of the extracerebral layer was 10.2 mm and 11.2 mm for animal 1 and 2, respectively.

Metrics

Table 1

The three moments used in DTOF analysis, along with their formula and the abbreviations for their sensitivity factors

Name

Related moment

Formula

Sensitivity factor

Attenuation

zeroth moment (area under the curve)

A=ln(m0)

MPP

Mean time of flight

first normalized moment

〈t〉=m1/m0

MTSF

Variance

second centralized moment

V=m2/m0−(m1/m0)2

VSF

Table 2

Percent change in the blood flow indices (TTP and dBF) obtained by analysis of attenuation (ΔA) and variance (ΔV) of DTOF during hypocapnia. Measurements were obtained directly on the brain and on the contralateral scalp. The error values are relative to the CBF change measured by CT perfusion (CTP). The thickness of the extracerebral layer was 10.2 mm and 11.2 mm for animal 1 and 2, respectively.

Animal #1

Animal #2

Percent Change

Error

Percent Change

Error

Ipsilateral (brain)

CTP brain

−32.0%

-

−44.4%

-

CTP scalp

-

-

-

-

ΔA TTP

−16.7%

15.3%

10.5%

54.9%

ΔV TTP

−21.1%

10.9%

4.5%

48.9%

ΔA dBF

−28.0%

3.9%

−45.5%

−1.1%

ΔV dBF

−31.6%

0.4%

−42.3%

2.1%

Contralateral (scalp)

CTP brain

−31.7%

-

−42.2%

-

CTP scalp

−19.1%

-

−29.3%

-

ΔA TTP

−16.7%

15.1%

−22.2%

20.0%

ΔV TTP

−20.0%

11.7%

−26.3%

15.9%

ΔA dBF

−20.9%

10.9%

−27.4%

14.8%

ΔV dBF

−31.6%

0.1%

−42.7%

−0.5%

Tables (2)

Table 1

The three moments used in DTOF analysis, along with their formula and the abbreviations for their sensitivity factors

Name

Related moment

Formula

Sensitivity factor

Attenuation

zeroth moment (area under the curve)

A=ln(m0)

MPP

Mean time of flight

first normalized moment

〈t〉=m1/m0

MTSF

Variance

second centralized moment

V=m2/m0−(m1/m0)2

VSF

Table 2

Percent change in the blood flow indices (TTP and dBF) obtained by analysis of attenuation (ΔA) and variance (ΔV) of DTOF during hypocapnia. Measurements were obtained directly on the brain and on the contralateral scalp. The error values are relative to the CBF change measured by CT perfusion (CTP). The thickness of the extracerebral layer was 10.2 mm and 11.2 mm for animal 1 and 2, respectively.